New Optically Active 2H-Azirin-3-amines as Synthons for Enantiomerically Pure 2,2-Disubstituted Glycines

Abstract

The synthesis of novel 2,2-disubstituted 2H-azirin-3-amines with a chiral amino group is described. Chromatographic separation of the diastereoisomer mixture yielded the pure diastereoisomers (1'R,2R)-4a-e and (1'R,2S)-4a-e (Scheme 1, Table 1), which are synthons for the (R)- and (S)-isomers of isovaline, 2- methylvaline, 2-cyclopentylalanine, 2-methylleucine, and 2-(methyl)phenylalanine, respectively. The configuration at C(2) of the synthons was determined by X-ray crystallography relative to the known configuration of the chiral auxiliary group. The reaction of 4 with thiobenzoic acid, benzoic acid, and the dipeptide Z-Leu-Aib-OH (12) yielded the monothiodiamides 10, the diamides 11 (Scheme 2, Table 3), and the tripeptides 13 (Scheme 3, Table 4), respectively.